Objective – To investigate the potential use of nerve allografts using a short term combined protocol of anti-lymphocyte serum (ALS) and cyclosporine (CsA) to improve nerve regeneration. Study Design – A rat sciatic nerve model was used. 15 male Lewis and 15 Lewis-Brown-Norway (LBN) rats were randomly divided into 3 groups. Group 1: control Lewis rats underwent the creation of a 1.5 cm deficit with conventional epineural repair with allografts from LBN rats without treatment. Group II: Lewis rats had a 1.5 cm deficits with LBN allograft repair and treatment with CsA for 3 weeks. Group III: Lewis rats sustained 1.5 cm deficits with LBN allograft repair and treatment with ALS and CsA for 3 weeks. Methods – Nerve regeneration was evaluated at 6 and 12 weeks by somatosensory evoked potentials (SSEP) and standardized pin-prick and toe-spread tests. Nerve samples were harvested at 12 weeks and were stained with toluidine blue to assess the total number of myelinated axons, axon area, and myelin sheath thickness. Each animal served as its own control to derive a ratio of operated versus normal outcome for SSEP and muscle weights. Results – No significant difference was found in somatosensory evoked potentials between the SSEP ratios of operated versus non-operated legs among the three groups using Dunn’s multiple comparison procedure with a Bonferroni correction. There was a significant (p<.05) median decrease in muscle denervation atrophy of nontreatment animals compared to CsA treated animals as evidenced by a greater gastrocnemius weight ratio. Functional outcome based upon toe-spread and pin-prick tests displays a trend towards better functional outcome for the ALS/CsA treatment group and preliminary histological analysis reveals a greater axon number and myelin sheath thickness for the ALS/CsA treatment group. Conclusions – In this preliminary study, peripheral nerve repair using allografts and a combined treatment protocol of ALS/CsA resulted in better functional recovery and morphometric outcome without a significant difference in electrophysiologic status compared to the nontreatment allograft group. This technique may provide an expanded source of nerve tissue to circumvent the morbidity of harvesting peripheral nerve autografts from multiple sites for those afflicted with extensive peripheral nerve injuries.